Fear conditioning is an excellent model system for understanding how the brain responds to threat. When organisms learn that an auditory cue predicts danger, the formation of this emotional memory requires plastic changes at synapses in the amygdala. Importantly, the subsequent retrieval and use of this memory involves activity-dependent synaptic destabilization. The functional significance of memory destabilization at retrieval is yet to be fully understood, but this process is likely to be important for memory updating and flexibility under normal conditions. Understanding and control of memory destabilization may open new avenues for clinical interventions in anxiety disorders. Our recent work has focused on the critical role of the ubiquitin-proteasome system (UPS) in controlling synaptic stability when existing memories are recalled. While destabilization is well documented at amygdala synapses, very few data exist related to the factors that control this process. In this project we use optogenetic silencing and stimulation to control neural activity during memory retrieval in behaving animals while quantifying biochemical signals related to destabilization in the amygdala. These signals include proteasome activity and activity-driven phosphorylation of Rpt6 regulatory subunits. Aim 1 is focused on altering activity within specific amygdala nuclei or connections. Studies in Aim 2 assess the role of prelimbic medial prefrontal cortex (PL) activity in triggering memory destabilization and address functional interactions between PL and the amygdala. In Aim 3 we address the role of the ventral periaqueductal gray and some of its reciprocal connections with the amygdala. The knowledge gained here may ultimately be applied to the targeted destabilization and erasure of traumatic memories.